Post-Translational Regulation of the Activity of ERK/MAPK and PI3K/AKT Signaling Pathways in Neuroblastoma Cancer

Abstract

Pathogenesis of cancer is a multi-step process containing a number of cellular alterations such as post-translational dysregulation of intracellular signaling proteins. These alterations control several functions in carcinogenesis such as angiogenesis, metastasis, evading growth suppressors, and sustaining proliferative signaling. Data of various studies has demonstrated that Phosphatidylinositol 3-kinase (PI3K/AKT) and Mitogen-activated protein kinase (ERK/MAPK) pathways are both abnormally activated in many cancer types, including neuroblastoma. ERK/MAPK and PI3K/AKT signaling pathways that are regulated by sequential phosphorylation upon extracellular stimulation have many important functions in cell cycle, migration, proliferation and apoptosis. Besides their aberrant phosphorylation/activation, there is a crosstalk between these two pathways resulting in an anti-apoptotic effect. In this chapter, carcinogenetic abnormalities in post-translational regulation of the activity of ERK/MAPK and PI3K/AKT pathways in neuroblastoma and other cancers will be summarized. In addition, several crosstalk nodes between two pathways will be briefly explained. All these concepts are not only crucial for thoroughly understanding the molecular basis of carcinogenesis but also choosing the appropriate molecular targets for effective diagnosis and treatment.

Gene expression profile of mitogen-activated kinases and microRNAs controlling their expression in HaCaT cell culture treated with lipopolysaccharide A and cyclosporine A

“…Disruptions in MAP kinase pathways play a key role in the course of psoriasis, influencing the induction and development of the inflammatory process, regulating the synthesis of pro-inflammatory cytokines and influencing the expression of genes encoding proteins that participate in the transmission of these signals [ 2 ]. It should be noted that research is already being carried out on blocking MAPK-dependent signaling pathways at various levels of the signaling cascade in different diseases, including rheumatoid arthritis [ 36 ], melanoma [ 6 ], neuroblastoma [ 12 ], Alzheimer’s disease [ 37 ], cardiovascular disease [ 38 ].…”

“…They participate in transmitting signals into the cell interior through a cascade of reactions, resulting in the activation of a number of proteins. In this way, MAPKs-dependent signaling pathways exert a modulatory effect on the expression of transcription factors, protein biosynthesis, cell division, and differentiation, and also influence cell survival and apoptosis [ 12 ]. MAPKs can be divided into three groups: extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinases (JNKs), and p38 MAPKs [ 13 ].…”

Expression profile of mRNAs and miRNAs related to mitogen-activated kinases in HaCaT cell culture treated with lipopolysaccharide a and adalimumab

“…They function in transmitting signals within the cell through a series of reactions, leading to the activation of various proteins. Consequently, MAPKs-dependent signaling pathways exert regulatory effects on transcription factors, protein synthesis, cell division, differentiation, and impact cell survival as well as apoptosis [ 2 ]. MAPKs can be categorized into three groups: 1) extracellular signal-regulated kinases (ERKs), 2) c-Jun N-terminal kinases (JNKs), and 3) p38 MAPKs [ 3 ].…”